Mr Yakovlev, who announced at the end of last month that he would stand in the St Petersburg elections for governor on May 19, handed in his notice last Friday.
His resignation is effective only until the results are in for the gubernatorial poll.
St Petersburg Mayor Anatoly Sobchak accepted Mr Yakovlev's resignation.
Mr Sobchak did not comment on whether or not Mr Yakovlev would be reinstated after the election should his deputy fail to win the election.
Mr Sobchak currently enjoys a lead of over 30 percentage points over all comers for the election. (SPP)